The T-even bacteriophage - E. coli system will be investigated as a model system of viral invasion, viral structure and viral assembly. Recent experiments have shown that polyglutamate derivatives of folic acid play a critical role in virus assembly and have also demonstrated that folic acid metabolism is controlled by the viral genome. Work will be devoted to determine: 1) How viral genes control folate metabolism in the infected cell; 2) How folates are used for viral assembly; 3) How two enzymes, dihydrofolate reductase and thymidylate synthetase are used for the assembly of the viral tail structure; 4) How the phage contractile tail sheath protein is assembled and how it functions in delivering DNA into the host cell; and 5) How polar bonds involving a C-terminal arginine residue on a viral tail protein stabilizes the virus structure. It is hoped the detailed chemical knowledge gained from these studies will lead to the control of virus assembly and to new principles involving assembly of other virus particles, including those causing human diseases.